Field of the Invention
The present invention relates to methods and apparatus for multi-spectral imaging. The methods and apparatus may be applied, for example, in cancer detection and localization. Some embodiments can perform rapid multispectral imaging in the visible/NIR spectrum suitable for quantitative image-based determination of tissue physiological and morphological properties.
Background
Real-time monitoring and imaging of tissue physiological and morphological changes provides very useful information for diagnosis and therapy. For example, during endoscopic imaging such information could be of prime importance for detecting different pathologies, especially in the early stages, such as cancer and ischemia. Spectral images obtained during endoscopy could be used to derive information about tissue physiological and morphological properties. However, the variation in measurement geometry, the loss of absolute intensity measurements, light-tissue interaction complexity, and analysis computation costs make the measurement and quantification of true physiological and morphological properties difficult in terms of accuracy and processing time.
Conventional endoscopy uses white light reflectance images to view surface morphology and assess internal organs based on appearance such as, tissue color and surface morphology. While changes in physical appearance (e.g. color and morphology) are useful, in order to accomplish more reliable and earlier detection of cancer and other diseases, a number of research groups have investigated the use of tissue auto-fluorescence to improve the detection sensitivity of cancerous lesions. Unfortunately auto-fluorescence imaging improves detection sensitivity at the cost of reduced detection specificity. This can result in increased medical costs due to the enlarged number of biopsies as a result of an increased number of false positives. Increases in the frequency of biopsies also increase the morbidity to patients.
In order to achieve high diagnostic sensitivity and high specificity, some research has studied point spectroscopy modalities such as reflectance, fluorescence, and Raman spectroscopy, or “point” microscopic imaging modalities such as confocal microscopy, optical coherence tomography, and multi-photon excitation imaging, as additional techniques to be combined with white light and fluorescence imaging.
U.S. Pat. No. 6,898,458 to Zeng at al. discloses an apparatus and method for simultaneous imaging and non-contact point spectroscopy measurements in both the white light reflectance and fluorescence modes. The noncontact spectral measurement and imaging may be performed by placing a specially designed spectral attachment between the endoscope eyepiece and the camera. The image and the spectrum are simultaneously displayed on a monitor for observing by an operator.
United States Patent Application Publication 2009/0270702 to Fawzy et al. describes a method for analyzing reflectance spectra to obtain quantitative information about cancer-related changes such as micro-vascular blood volume fraction in tissue, tissue blood oxygen saturation (physiological parameters) as well as tissue scattering micro-particle volume fraction and size distribution (morphological parameters). Both of the above references describe conducting spectral measurements though the eyepiece of a fiber endoscope. The spectral measurements involved point spectroscopy as opposed to spectral imaging.
Absorption characteristics and scattering characteristics of light differ according to the wavelength of the light. These differences are due to a distribution of different absorbent material such as blood vessels in the depth direction. Longer wavelengths of illumination light, such as infrared light, provide information from deeper parts of the tissue while shorter wavelengths of illumination light give information from the tissue near the surface. Detection of changes that occur near the tissue surface is essential for early cancer detection.
Several groups have reported intrinsic differences in optical absorption and scattering properties between malignant and benign lesions/normal tissues and have related these changes directly to tissue physiological and morphological changes that occur during cancer transformations. See M. P. L. Bard, A. Amelink, V. N. Hegt, W. J. Graveland, H. J. C. M. Sterenborg, H. C. Hoogsteden, J. G. J. V. Aerts, “Measurement of Hypoxia-related parameters in bronchial mucosa by use of optical spectroscopy”, Am. J. Respir. Crit. Care Med., 171, 1178-1184, 2005; G. Zonios, L. T. Perelman, V. Backman, R. Manoharan, M. Fitzmaurice, J. Van Dam, and M. S. Feld, “Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo”, Appl. Opt. 38, 6628-6636, 1998; B. Beauvoit, and B. Chance, “Time-resolved spectroscopy of mitochondria, cells and tissue under normal and pathological conditions”, Mol Cell Biochem., 184, 445-455, 1998; J. R. Mourant, T. M. Johnson, and J. P. Freyer, “Characterizing mammalian cells and cell phantoms by polarized backscattering fiber-optic measurement”, Appl. Opt. 40, 5114-5123, 2001; J. R. Mourant, A. H. Hielscher, A. A. Eick, T. M. Johnson, and J. P. Freyer, “Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells”, Cancer, 84, 366-374, 1998; H. Zeng, C. MacAulay, B. Paclic, and D. I. McLeant, “A computerized auto-fluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies”, Phys. Med. Biol. 38, 231-240, 1993; R. J. Nordstorm, L. Burke, J. M. Niloff, and J. F. Myrtle, “Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy”, Lasers Surg. Med. 29, 118-127, 2001; I. Georgakoudi, E. E. Sheets, M. G. Muller, V. Backman, C. P. Crum, K. Badizadegan, R. R. Dasari, and M. S. Feld, “Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo”, Am J Obstet Gynecol 186, 374-381, 2002; M. G. Muller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Layer, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, and M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma”, Cancer 97, 1681-1692, 1997; M. P. L. Bard, A. Amelink, M. Skurichina, M. den Bakkerd, S. A. Burgers, J. P. van Meerbeeck, R. P. W. Duin, J. G. J. V. Aerts, H. C. Hoogsteden, and H. J. C. M. Sterenborg, “Improving the specificity of fluorescence bronchoscopy for the analysis of neoplastic lesions of the bronchial tree by combination with optical spectroscopy: preliminary communication”, Lung Cancer 47, 41-47, 2005. The reflectance spectral measurements by all of these groups were conducted using a fiber optic probe inserted through the endoscope instrument channel. In addition the optic probe must be placed in contact with the tissue surface. These types of fiber optic probe measurement geometry are dramatically different from the imaging geometry (broad beam illumination and narrow spot detection).
Various groups have investigated multi-spectral or hyperspectral imaging for studying tissue pathology. For example, G. N. Stamatas, M. Southall and N. Kollias, “In vivo monitoring of cutaneous edema using spectral imaging in the visible and near infrared”, J. Invest. Dermatol. 126, 1753-1760, 2006; and G N. Stamatas, N. Kollias, “Noninvasive quantitative documentation of cutaneous inflammation in vivo using spectral imaging”, SPIE Proceedings 6078, 60780P, 2006, describe use of spectral imaging to obtain in vivo 2-D maps of various skin chromophores including oxy- and deoxy-hemoglobins. They use 18 narrow band filters to obtain images in the 400-970 nm range. A phase correction algorithm was then used to align the individual images at different wavebands to fight motion artifacts.
A state of the art endoscopic hyperspectral imaging system has been reported by the Farkas group. See U.S. Pat. No. 5,796,512 to Farkas et al.; D. L. Farkas and D. Becker, “Applications of spectral imaging: detection and analysis of human melanoma and its precursors”, Pigment Cell Res., 14, 2-8, 2001; E. Lindsley, E. S. Wachman and D. L. Farkas, “The hyperspectral imaging endoscope: a new tool for in vivo cancer detection”, SPIE Proceedings, 5322, 75-82, 2004; and A. Chung, S. Karlan, E. Lindsley, S. Wachsmann-Hogiu and D. L. Farkas, “In vivo cytometry: a spectrum of possibilities”, Cytometry Part A, 69A, 142-146, 2006. Their system acquires parallel and perpendicular polarized images at 32 evenly spaced bands from 380-690 nm in 0.25 seconds. A monochromator or AOTF (acousto-optic tunable filter) based tunable light source and a single high speed CCD camera was used for image acquisition. A 2.0 mm size catheter comprising an illumination fiber and two imaging fiber bundles was passed through the instrument channel to perform the hyperspectral imaging. This group used algorithms developed for fiber-probe point reflectance spectral analysis to analyze the imaging spectral data to derive a scatter size parameter image. In clinical tests, the system encountered problems from specular reflection interference and motion artifacts due to movement from either endoscope or patient.
Another system is disclosed in International Patent Application Publication WO2009/052607 to Fawzy which describes a method for quantifying tissue de-oxygenated blood index directly from images that are taken by illuminating the tissue with two different wavelength bands sequentially.
U.S. Pat. No. 7,729,751 to Ayame et. al. and United States Patent Application Publication 2009/0023991 to Gono et al. disclose methods to improve the visualization of the tissue color tone changes using the “electronic spectral imaging” technique (color correction techniques). “Electronic spectral imaging” is based on an estimation of reflectance spectra from RGB images or narrow band images using samples of the spectra which were measured a priori. “Electronic spectral imaging” does not provide accurate representations of true tissue reflectance properties and tissue physiology and morphology.
United States Patent Application Publication 2007/0024946 to Panasyuk et al. discloses a multispectral imaging system and method for real-time or near real-time assessment of tissue oxygen saturation, delivery and extraction during shock and resuscitation. In this system, spectral images are obtained by sequential illumination using different wavelengths.
There remains a need for cost-effective apparatus and methods for rapid multispectral imaging.